Significant differences in access to tests and treatments for multiple myeloma between public and private systems in Latin America. Results of a Latin American survey. GELAMM (Grupo de Estudio Latino Americano de Mieloma Múltiple).

The incidence of multiple myeloma (MM) has increased in the last 20 years, particularly in middle and low-middle income countries. Access to diagnostic and prognostic tests and the availability of effective care is highly variable globally. Latin America represents 10% of the world population, distributed in countries of varied size, population, and socio-economic development. In the last decade, great improvements have been made in the diagnosis and treatment of MM. Applying these advances in real life is a challenge in our region. Local data regarding MM standards of care and outcomes are limited. A survey was carried out among hematologists from 15 Latin American countries to describe access to MM diagnostic and prognostic tests and the availability of effective care options. This study provides real-world data for MM in our region, highlighting striking differences between public and private access to essential analyses and therapeutic options.

Phase 3 trial of three thalidomide-containing regimens in patients with newly diagnosed multiple myeloma not transplant-eligible.

The introduction of agents such as thalidomide, lenalidomide, and bortezomib has changed the management of patients with multiple myeloma who are not eligible for autologous transplantation, many of whom are elderly. We sought to compare three thalidomide-based oral regimens among such patients in Latin America. We randomized patients with newly diagnosed multiple myeloma with measurable disease to one of the following regimens: melphalan, prednisone, and thalidomide (MPT); cyclophosphamide, thalidomide, and dexamethasone (CTD); and thalidomide and dexamethasone (TD). The TD arm was closed prematurely and was analyzed only descriptively. The primary endpoint was the overall response rate (ORR), whereas progression-free survival (PFS) and overall survival (OS) were secondary endpoints. The accrual rate was slower than expected, and the study was terminated after 82 patients had been randomized. The ORRs were 67.9 % with MPT, 89.7 % with CTD, and 68.7 % with TD (p = 0.056 for the comparison between MPT and CTD). The median PFS was 24.1 months for MPT, 25.9 months for CTD, and 21.5 months for TD. There were no statistically significant differences in PFS or OS between MPT and CTD. In an unplanned logistic regression analysis, ORR was significantly associated with treatment with CTD (p = 0.046) and with performance status of 0 or 1 (p = 0.035). Based on the current results, no definitive recommendations can be made regarding the comparative merit of the regimens tested. Nevertheless and until the results of further studies become available, we recommend either CTD or MPT as suitable frontline regimens for patients with multiple myeloma who are not candidates to transplantation in settings where lenalidomide and bortezomib are not available.

Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group.

Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10(9)/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be re-examined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL.

New recurrent chromosome alterations in patients with multiple myeloma and plasma cell leukemia.

Chromosome abnormalities detected in metaphases from multiple myeloma (MM) cells have a clear impact on prognosis and response to therapy. Thirteen out of 50 (26%) patients with plasma cell disorders and abnormal karyotypes (11 with MM and 2 with plasma cell leukemia (PCL)) were selected for inclusion in the present report based on the presence of karyotypes with new and/or infrequent structural aberrations. Thirty-three new rearrangements, including a novel recurrent aberration: psu dic(5;1)(q35;q10), were detected. Chromosome 1 was the most frequently involved. Gains of genetic material (57%) were noted more frequently than losses (43%). Three rearrangements that were observed only once in the literature appear to be recurrent from our data: del(16)(q13), del(5)(p13) and i(3)(q10), the latter being a single structural aberration in the karyotype. Clinical parameters from our series were compared with 2 control groups: 20 MM cases with recurrent aberrations in MM/PCL with a similar distribution of abnormalities associated with poor prognosis (group 1), and 40 with normal karyotypes and fluorescence in situ hybridization analysis (group 2). Significantly increased serum calcium levels (p = 0.022) in patients with new and/or infrequent chromosome changes with respect to both control groups, and a higher percentage of bone marrow plasma cell infiltration (p = 0.005), ß(2) microglobulin, and lactate dehydrogenase levels (p < 0.0001) compared to group 2 were observed. Our results suggest that some of these novel rearrangements may be capable to deregulate genetic mechanisms related to the development and/or progression of the disease. The finding of new recurrent aberrations supports this hypothesis.

Esplenectomía laparoscópica y mano asistida / Laparoscopic splenectomy and hand assited

Antecedentes: Las publicaciones sobre esplenectomías laparoscópicas (EL) son poco frecuentes, y el número de pacientes limitado por la baja prevalencia de las esplenopatías que requieren tratamiento quirúrgico. Sin embargo para algunas que requieren la remoción del bazo, es considerada la técnica de elección. Objetivo: Evaluar la experiencia realizada en el Hospital Italiano de Buenos Aires, con las técnicas endoscópicas de remoción esplénica. Diseño: Descriptivo retrospectivo. Institución: Hospital de Comunidad. Servicio de Cirugía General. Población: Entre junio de 1995 y marzo de 2001 fueron realizadas esplenectomías laparoscópicas a 25 pacientes, 68 por ciento de sexo femenino con una edad promedio de 47 años (r:19-81). La patología subyacente fue: púrpura trombocitopénica idiopática (P.T.I) en 15, síndromes linfoproliferativos en 6, esferocitosis en 2, anemia hemolítica auto inmune en 1, esplenomegalia de causa no aclarada en 1. Métodos: Se utilizó la posición en decúbito lateral derecho, usando entre 3 y 4 trocares; el pedículo esplénico se ocluyó con clips y nudos intra o extra corpóreos. No se usaron suturas mecánicas. El bazo se colocó en una bolsa abdominal, extrayéndolo fragmentado por el ombligo. En la técnica mano asistida se utilizó el sistema Hand Port (Smith & Nephew), por el hipocondro derecho para la introducción de la mano no dominante del cirujano. Resultados: Se debió convertir en 3 casos (12 por ciento) por complicaciones hemorrágicas (2) y adherencias firmes al hígado (1). En el abordaje laparoscópico, el tiempo promedio de cirugía fue de 170 minutos (r:110-270), la internación promedio de 3 días (r:1-5), y el peso promedio del bazo de 300 gramos (r:59-500). En cinco casos se resecaron bazos accesorios. En el abordaje mano asistido (2 casos), el tiempo promedio de cirugía fue de 80 minutos, la internación promedio de 2,5 días (r:2-3), y el peso promedio del bazo de 1200 gramos (r:1150-1250). Tres pacientes (12 por ciento) presentaron complicaciones (1 neumotórax, 1 hematoma subfrénico, 1 absceso subfrénico todos de localización izquierda). Ninguno debió ser reoperado. En el seguimiento alejado 2 pacientes presentaron recurrencia de su enfermedad asociada a patología sistemática de base. Uno de ellos tenía un bazo accesorio que fue resecado por vía laparoscópica...

[Acute promyelocytic leukemia: experience with trans-retinoic acid in Argentina]. / Leucemia promielocítica aguda: Experiencia argentina con ácido trans-retinoico.

From February 1992 to February 1995, 77 patients with APL were treated with ATRA in induction (59 patients de novo, 6 in first relapse, 1 with APL secondary to a mielodisplastic syndrome). The dose used was 45 mg/k/day-30 mg/k/day until complete remission (CR) was achieved; of the 66 evaluable patients, 50 achieved complete remission (78%). Among the 14 patients who did not attain CR, 13 died, 10 of bleeding episodes and 3 of retinoic syndrome; one was rescued with chemotherapy. We proposed consolidation treatment with high dose Ara-C and Idarubicin to the 49 patients in complete remission; 6 could not receive it and 5 died; the disease free survival period of the other patients was 81% (CI95 90%-66%) at one year and 74% (CI95 91%-52%) at two years. We consider that our results are similar to those of other groups and we are inclined to continue with this treatment protocol.

[Adult HTLV-I positive leukemia-lymphoma in Argentina]. / Leucemia-linfoma T del adulto HTLV-I positiva en Argentina.

Human T-cell lymphotropic virus type I (HTLV-I) is associated with adult T-cell leukaemia/lymphoma (ATLL) and tropical spastic paraparesis (TSP/HAM) in endemic and non-endemic areas. Serological studies have shown that HTLV-I is prevalent in some Latin American countries such as Brasil, Chile, Colombia, Perú and Uruguay. We describe here the clinical and laboratory features of five cases of ATLL diagnosed in Argentina. All patients (4 males, 1 female; median age 48.2 years) were of caucasian origin; 4 born in Argentina and 1 in Chile. High risk factors for HTLV-I infection were not apparent in Argentina patients, whereas the Chilean resident, who was a promiscuous heterosexual, travelled through Chile frequently. Positive results for antibodies to HTLV-I were detected in all five cases and in some of their relatives. This report suggests that HTLV-I infection may be endemic in, Argentina where TSP has also been described.

La biopsia percutánea en las lesiones genitourinarias / Percutaneous biopsy in genitourinary lesions

Presentamos nuestra experiencia sobre una población de 113 pacientes (80 varones y 33 mujeres) examinados entre febrero de 1984 y julio de 1990. La edad promedio del conjunto fue de 46 años con un rango etario comprendido entre 23 y 76 años. El procedimiento fue realizado en forma ambulatoria. Se utilizó para guiar las punciones la Ecografía y la TC. El tamaño de las lesiones varió entre 1 y 12 cm. predominando las menores de 5 cm. La biopsia confirmó la existencia de tumores en el 78 por ciento de los casos. Se registraron seis complicaciones. La biopsia percutánea es un método efectivo y de baja morbilidad para confirmar la etiología de lesiones orgánicas. La discriminación anatómica de la ecografía y la TC permite biopsar lesiones grandes y pequeñas en diversas localizaciones

[Myelodysplastic syndrome: experience of the Study and Treatment of Bone Marrow Failure Group]. / Sindromes mielodisplásticos: experiencia del Grupo de Estudio y Tratamiento de las Insuficiencias Medulares (GETIM).

Myelodysplastic syndromes (SMD) were studied in 58 patients (37 men, 21 women; mean age 61 years, range 18-81) who were grouped according to FAB criteria (Table 1). None of them showed a secondary SMD to medullary toxic agents or cytostatic treatments although 5 presented concomitant neoplastic disease. Morphologic alterations in peripheral blood smears and bone marrow were registered by 3 hematologists working independently. The intracellular and extracellular iron deposits were evaluated in every case with Perls; peroxidase activity was determined in 16 patients and intraleucocitary alkaline phosphatase reaction was carried out in 17 patients. Twenty five patients (43%) had refractory anemia (RA); 10 (17%) sideroblastic anemia; 13 (25%) refractory anemia with excess of blasts (AREB); 3 (5%) AREB in transformation (AREB-T) and 7 myelomonocytic leukemia (LMMC). Clinical manifestations at diagnosis are described in Table 2. In the observation period there were cases of anemia requiring transfusion, bacterial infections, muco-cutaneous hemorrhage and hemorrhagic episodes in the central nervous system. In the bone marrow smears the cellularity was normal or increased in 53 cases and diminished in only 3. The degree of dysplastic characteristics (erythroid, granulocytic and megakaryocytic) ranged from low to severe. It was low in most of AR, being the erythroid population the most affected in AS and the granulocytic one in AREB and AREB-T. Patients with LMMC showed similar characteristics to those with myeloproliferative syndromes and the differential diagnosis were sometimes difficult, accounting for their separate inclusion in Table 4. Out of 23 patients, 5 presented clonal pathology detected in cytogenetic studies.(ABSTRACT TRUNCATED AT 250 WORDS)